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Possibilities of treatment of patients with castrationrefractory prostate cancer using enzalutamide

https://doi.org/10.21518/2079-701X-2019-19-176-180

Abstract

Prostate cancer is one of the most actual oncourological diseases because of the persisting high rates of morbidity and mortality from this pathology. More than 1 100 000 new cases of this pathology are registered in the world every year. The incidence of prostate cancer in the Russian Federation continues to increase steadily. Despite the success in early detection of this disease, primarily due to the introduction of diagnostics with the use of a specific prostatic antigen, the frequency of detection of primary metastatic cancer of the prostate gland remains high and is about 20%. Metastatic castration-resistant prostate cancer is an extremely heterogeneous disease with an unfavorable prognosis in most of these patients, which requires a differentiated approach when prescribing therapy in each case. Despite the standard approach to prescribing chemotherapy as one of the main methods of drug treatment, the method of hormonal therapy of the second line using drugs aimed at the androgenic mechanism of cellular proliferation regulation is an effective and less toxic option. A fundamentally different mechanism of action has a new drug hormonal therapy of the second line enzalutamide, which is able to selectively block androgen receptors and disturb the translocation of the signal from the receptor into the cell and the cell nucleus. A number of large randomized trials that studied the effectiveness of this drug have allowed to register it for clinical use, including in our country. The article presents a review of the literature on the use of enzalutamide in patients with metastatic castration-refractory prostate cancer, as well as a description of the clinical case of the use of this drug in real practice.


About the Authors

B. Ya. Alekseyev
National Medical Research Radiological Centre
Russian Federation

Dr. of Sci. (Med), Professor, Deputy Director General for Scientific Work

3, 2nd Botkinskiy proezd, Moscow, 125284, Russian Federation



K. M. Nyushko
P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation
Russian Federation

Cand. of Sci. (Med), Leading Researcher of the Department of Tumors of Reproductive and Urinary Organs

3, 2nd Botkinskiy proezd, Moscow, 125284, Russian Federation



A. D. Kaprin
National Medical Research Radiological Centre
Russian Federation

Academician of the RAS, Dr. of Sci. (Med), Professor, General Director

3, 2nd Botkinskiy proezd, Moscow, 125284, Russian Federation



References

1. Kaprin A.D., Starinskiy V.V., Petrova G.V. (eds). Cancer statistics in Russia in 2017. Moscow: Gertsen P.A. Moscow Cancer Research Institute – filial of TSYB Medical Radiological Research Center of the Ministry of Health of Russia; 2018. (In Russ.) Available at: http://www.oncology.ru/service/statistics/malignant_tumors/2017.pdf.

2. Deng Y., Bi R., Zhu Z., et al. A Surveillance, Epidemiology and End Results database analysis of the prognostic value of organ-specific metastases in patients with advanced prostatic adenocarcinoma. Oncol Lett. 2019;18(2):1057-1070. doi: 10.3892/ol.2019.10461.

3. Teo M.Y., Rathkopf D.E., Kantoff P. Treatment of Advanced Prostate Cancer. Annu Rev Med. 2019;70:479-499. doi: 10.1146/annurevmed-051517-011947.

4. Pham T., Sadowski M.C., Li H., et al. Advances in hormonal therapies for hormone naïve and castration-resistant prostate cancers with or without previous chemotherapy. Exp Hematol Oncol. 2016;5:15. doi: 10.1186/s40164-016-0046-1.

5. Lebret T., Ruffion A., Latorzeff I., et al. Criteria for indication and treatment modification in a cohort of patients with prostate cancer treated with hormone therapy. Eur Urol. 2017;72(1):118-124. doi: 10.1016/j.eururo.2017.03.020.

6. Sartor O. Advanced prostate cancer update 2018. Eur Urol. 2017;72(1):118-124. doi: 10.1016/j.eururo.2017.03.020.

7. Oh W. Chemotherapy for patients with advanced prostate carcinoma: a new option for therapy. Cancer. 2000;88:3015-3021. doi: 10.1002/1097-0142(20000615)88:12+3015::aidcncr18>3.0.co;2-m.

8. Tannock I.F., de Wit R., Berry W.R., et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502-12. doi: 10.1056/NEJMoa040720.

9. de Bono J.S., Oudard S., Ozguroglu M., et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376(9747):1147-1154. doi: 10.1016/S0140-6736(10)61389-X.

10. de Bono J.S., Logothetis C.J., Molina A., et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995-2005. doi: 10.1056/NEJMoa1014618.

11. Ryan C.J., Smith M.R., de Bono J.S., et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138-48. doi: 10.1056/NEJMoa1209096.

12. Attard G., Belldegrun A.S., de Bono J.S. Selective blockade of androgenic steroid synthesis by novel lyase inhibitors as a therapeutic strategy for treating metastatic prostate cancer. BJU Int. 2005;96(9):1241-1246. doi: 10.1111/j.1464-410X.2005.05821.x.

13. Tran C., Ouk S., Clegg N.J., et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009;324:787-790. doi: 10.1126/science.1168175.

14. Chen C.D., Welsbie D.S., Tran C., et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med. 2004;(10):33-39. doi: 10.1038/nm972.

15. Paul R., Breul J. Antiandrogen withdrawal syndrome associated with prostate cancer therapies: incidence and clinical significance. Drug Saf. 2000;23(5):381-390. doi: 10.2165/00002018-200023050-00003.

16. Teutsch G., Goubet F., Battmann T., et al. Nonsteroidal antiandrogens: synthesis and biological profile of high-affinity ligands for the androgen receptor. J Steroid Biochem Mol Biol. 1994;48:111-119. doi: 10.1016/0960-0760(94)90257-7.

17. Van Dort M.E., Robins D.M., Wayburn B. Design, synthesis, and pharmacological characterization of 4-[4, 4-dimethyl-3-(4-hydroxybutyl)-5-oxo-2-thioxo-1- imidazolidinyl]- 2-iodobenzonitrile as a high-affinity nons- teroidal androgen receptor ligand. J Med Chem. 2000;43:33443347. doi: 10.1021/jm000163y.

18. Jung M.E., Ouk S., Yoo D., et al. Structureactivity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC). J Med Chem. 2010;53:2779-2796. doi: 10.1021/jm901488g.

19. Hodgson M.C., Astapova I., Cheng S., et al. The androgen receptor recruits nuclear receptor CoRepressor (N-CoR) in the presence of mifepristone via its N and C termini revealing a novel molecular mechanism for androgen receptor antagonists. J Biol Chem. 2005;280:6511-6519. doi: 10.1074/jbc.M806384200.

20. Baek S.H., Ohgi K.A., Nelson C.A., et al. Ligandspecific allosteric regulation of coactivator functions of androgen receptor in prostate cancer cells. Proc Natl Acad Sci U.S.A. 2006;103:3100-3105. doi: 10.1073/pnas.1815087116.

21. Efstathiou E., Titus M., Wen S., et al. Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol. 2015;67:53-60. doi: 10.1016/j.eururo.2014.05.005.

22. Guerrero J., Alfaro I.E., Gomez F., et al. Enzalutamide, an androgen receptor signaling inhibitor, induces tumor regression in a mouse model of castration-resistant prostate cancer. Prostate. 2013;73:1291-1305. doi: 10.1002/pros.22674.

23. Morris M.J., Basch E.M., Wilding G., et al. Department of Defense prostate cancer clinical trials consortium:a new instrument for prostate cancer clinical research. Clin Genitourin Cancer. 2009;7:51-57. doi: 10.3816/CGC.2009.n.009.

24. Bambury R.M., Scher H.I. Enzalutamide: Development from bench to bedside. Urol Oncol. 2015;33:280288. doi: 10.1016/j.urolonc.2014.12.017.

25. Scher H.I., Beer T.M., Higano C.S., et al. Antitumour activity of MDV3100 in castrationresistant prostate cancer: a phase 1-2 study. Lancet. 2010;375:1437-1446. doi: 10.1016/S0140-6736(16)31458-1.

26. Scher H.I., Fizazi K., Saad F. et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187-1197. doi: 10.1056/NEJMoa1207506.

27. Bennett D., Gibbons J.A., Mol R., et al. Validation of a method for quantifying enzalutamide and its major metabolites in human plasma by LC-MS/MS. Bioanalysis. 2014;6:737-744. doi: 10.4155/bio.13.325.

28. Shore N.D., Chowdhury S., Villers A., et al. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomized, double-blind, phase 2 study. Lancet Oncol. 2016;17(2):153-163. doi: 10.1016/S1470-2045(15)00518-5.

29. Beer T.M., Armstrong A.J., Rathkopf D.E. et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424-433. doi: 10.1056/NEJMoa1405095.

30. Fizazi K., Scher H.I., Miller K. et al. Effect of enzalutamide on time to first skeletal-related event, pain, and quality of life in men with castration- resistant prostate cancer: results from the randomised, phase 3 AFFIRM trial. Lancet Oncol. 2014;15:1147-56. doi: 10.1016/S1470-2045(14)70303-1.

31. Sternberg C.N., de Bono J.S., Chi K.N. et al. Improved outcomes in elderly patients with metastatic castration-resistant prostate cancer treated with the androgen receptor inhibitor enzalutamide: results from the phase III AFFIRM trial. Ann Oncol. 2014;25:429-434. doi: 10.1093/annonc/mdt571.

32. Saad F., de Bono J., Shore N. et al. Efficacy outcomes by baseline prostate- specific antigen quartile in the AFFIRM trial. Eur Urol. 2014;67:223-230. doi: 10.1016/j.eururo.2014.08.025.


Review

For citations:


Alekseyev BY, Nyushko KM, Kaprin AD. Possibilities of treatment of patients with castrationrefractory prostate cancer using enzalutamide. Meditsinskiy sovet = Medical Council. 2019;(19):176-180. (In Russ.) https://doi.org/10.21518/2079-701X-2019-19-176-180

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